The general idea for this protocol is based on a novel mechanism for the selective production of Nitric oxide from nitrite, using human hemoglobin as nitrate reductase. This reaction is favored in tissues with low oxygen tension and low pH, such as the environment most likely to occur at leg ulcer sites. This is an open label, Phase I study of topical sodium nitrite for subjects with leg ulcers, of more than 4 weeks duration, who have sickle cell disease or other hemolytic disorders. Twelve subjects with homozygous sickle cell disease (HbSS), sickle-thalassemia (Hb S- thalassemia) or HbSC, HBSD or other hemoglobinopathies or hemolytic disorders will be enrolled at the NIH Clinical Center. Four cohorts of subjects, with three subjects at each dose level, have been treated with escalating doses of topical sodium nitrite cream twice a week based on the modified Fibonacci schema. For dose levels 1 - 4, subjects will have 0.1 cm of sodium nitrite cream applied per 1 square cm of the ulcer. All subjects receive topical application of the drug twice a week for four weeks total. Three subjects are treated at each dose level. The subjects are evaluated at the Clinical Center to determine eligibility, obtain informed consent, detailed medical history and physical examination. A plain x-ray of the leg(s) involved is performed to rule out underlying osteomyelitis, which represents an exclusion criterion. Doppler ultrasound of the leg(s) is performed to assess the presence of venous insufficiency and/or thrombosis. Subjects have a detailed wound assessment performed by the wound ostomy continence nurse service (WOCN) to include a wound culture. A seven-day pain inventory tool and a quality of life assessment is completed prior to initiating therapy. Routine laboratory studies are obtained along with additional research laboratory tests at baseline and at specified times during the study. The subjects are then be scheduled for a 4-5-day inpatient hospitalization, in order to allow for extensive additional studies, and pharmacokinetics of nitric oxide, sodium nitrite and methemoglobin. The hospitalization facilitates close monitoring for safety of administration of sodium nitrite cream and the occurrence of side effects. While in the hospital, all subjects have the following baseline tests: laboratory assessments, measurement of the ulcers size, and a non-contrast MRI. Subjects then undergo infrared photography in order to measure the perimeter of the ulcers and to identify surface blood vessels that will guide the placement of wireless thermo-patches. Infrared and laser perfusion imaging are repeated throughout the study at defined time points. In order to assess histopathological changes in the skin of individuals who have sickle cell disease or other hemolytic disorders, one punch biopsy is performed in consenting subjects who have more than one leg ulcer and it is on the opposite leg as an optional part of their evaluation. If a subject declines participation in the biopsy portion of the study, he/she is not excluded from participation in the other portions of the study. The primary expected toxicity during this portion of the study, is low grade, asymptomatic methemoglobinemia, therefore, blood is tested for methemoglobin at each visit. At the completion of the 4 weeks of therapy, baseline studies are repeated on an outpatient basis. To date we have completed all original 12 subjects planned and an additional 6 subjects at an intermediate dose of 1.8%. No subject has suffered serious complications from the application of the cream and we have not observed dose-limiting methemoglobinemia. The cream seems to be well tolerated at each of the strengths used so far. we have observed a decrease in ulcer size by more than 25% in 80% of the subjects and three patients experienced a complete closure of their wounds. Moreover, we have observed a statistically significant decrease in pain at the ulcer size after application of study cream. Patients that had more than one ulcer did not experience the same degree of pain releif at the ulcers treated with standard of care alone.